Loss of Tet2 affects platelet function but not coagulation in mice  

作　　者：Bichen Wang Meijuan Xia Ting Chen Mengke Li Deyang Shi Xiaomin Wang Aiming Pang Jiaxi Zhou Weiping Yuan Yajing Chu 

机构地区：[1]State Key Laboratory of Experimental Hematology,National Clinical Research Center for Hematological Disorders,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin,China [2]Hematopoietic Stem Cell Transplantation Center,National Clinical Research Center for Hematological Disorders,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin,China

出　　处：《Blood Science》2020年第4期129-136,共8页血液科学（英文）

基　　金：This work was partially supported by the funds from the CAMS Innovation Fund for Medical Sciences(2016-I2M-1-017 and 2017-I2M-3-015);National Natural Science Foundation of China(81629001,81421002,81600136,81770105,81970149).

摘　　要：Ten-eleven translocation 2(TET2)functions as a methylcytosine dioxygenase that catalyzes the iterative oxidation of 5-methylcytosine to 5-hydroxymethylcytosine,5-formylcytosine and 5-carboxylcytosine.TET2 has been shown to be crucial for the maintenance and differentiation of hematopoietic stem cells,and its deletion and/or mutations results in the expansion of HSPCs,and leads to hematological malignancies.TET2 mutations were found in a variety of hematological disorders such as CMML(60%),MDS(30%),MPN(13%)and AML(20%).Interestingly,it was shown that CMML patients with TET2 mutation exhibited fewer platelets than CMML patients without TET2 mutation.However,the role and function of TET2 in platelet hemostasis and thrombogenesis is not well defined.Here in this study,using a genetically engineered Tet2 deletion mouse model,we found that the absence of Tet2 caused a decrease in the proportion of MEP cells and hyperploid megakaryocytes.Additionally,Tet2-deficient mice displayed impaired platelet activation and aggregation under stimulation of ADP and low concentrations of thrombin,although the modestly compromised platelet function and MEP differentiation in Tet2-deficient mice could be compensated without affecting blood coagulation function.Our study indicate that Tet2 deficiency leads to mild impairment of platelet function and thrombopoiesis in mice.

关 键 词：MEGAKARYOCYTES Mouse Mutation PLATELET Tet2 THROMBOSIS 

分 类 号：R55[医药卫生—血液循环系统疾病]